The present invention generally relates to atmospheric pressure chemical ionization (APCI) mass spectrometry (MS). More particularly, the present invention relates to an apparatus and method for improving vaporization of sample-containing droplets in the APCI source.
Mass spectrometry is a highly sensitive method of molecular analysis. In general, mass spectrometry is a technique that produces a mass spectrum by converting the components of a sample into rapidly moving gaseous ions, and resolving the ions on the basis of their mass-to-charge (m/e or m/z) ratios. The mass spectrum can be expressed as a plot of relative abundances of charged components as a function of mass, and thus can be used to characterize a population of ions based on their mass distribution. Mass spectrometry is often performed to determine molecular weight, molecular formula, structural identification, and the presence of isotopes. The apparatus provided for implementing mass spectrometry, i.e., the mass spectrometer (MS), typically consists of a sample inlet system, an ion source, a mass analyzer, and an ion detection system, as well as the components necessary for carrying out signal processing and readout tasks. Many of these functional components of the mass spectrometer, particularly the mass analyzer, are maintained at a low pressure by means of a vacuum system. The ion source converts the components of a sample into charged particles. The negative particles are ordinarily removed from the process flow. The mass analyzer disperses the charged particles based on their respective masses, and then focuses the ions on the detector. The ion currents produced by the detector are then amplified and recorded as a function of spectral scan time. The designs of the components of the mass spectrometer, and the principles by which they operate, can vary considerably. Thus, components of differing designs have distinct advantages and disadvantages when compared to each other, and the desirability of any one design can depend on, among other factors, the nature of the sample to be analyzed.
One type of sample inlet system can be described as being chromatographicxe2x80x94that is, in some types of analytical systems, the effluent from a chromatographic column can be utilized as the sample source for a mass spectrometer. Stated differently, the mass spectrometer in such cases can be considered as serving as the detector for the chromatographic apparatus. Such an arrangement is commercially available in systems in which a gas chromatographic (GC) apparatus is directly coupled to the mass spectrometer (GC/MS systems), or a liquid chromatographic (LC) apparatus is directly coupled to the mass spectrometer (LC/MS systems). These combined systems are particularly useful for deriving complex spectra from mixtures, as it is known that mass spectrometers alone are more or less limited to handling pure compounds and relatively simple mixtures.
An ion source commonly serving as the interface between an LC apparatus and the mass spectrometer operates according to the principle of atmospheric pressure chemical ionization (APCI). Simply stated, APCI is a means for ionizing samples dissolved in a liquid. Typically, the sample-containing liquid emitted from the LC apparatus is pneumatically nebulized into numerous small droplets, typically below 100 microns in diameter. Heat is applied to the droplets to vaporize the liquid and sample matrix, and the resulting vapor is subsequently passed through a low-current corona discharge. In the discharge, ion molecule reactions occur between the charge-neutral sample and the ions formed in the primary discharge. The ion molecule reactions with the sample cause the sample to become charged, and the charged sample ions are passed through an opening in a vacuum chamber into the mass analyzer of the mass spectrometer for mass analysis.
FIG. 1 illustrates an example of a conventional APCI source, generally designated 10, utilized in, for example, an LC/MS system. In general terms, APCI source 10 comprises an inlet section, generally designated 20; a vaporization section, generally designated 30; an ionization section, generally designated 40; and an outlet section, generally designated 50, that includes an aperture 53 through which ionized products are directed into the mass analyzer of the mass spectrometer. For simplicity, the mass analyzer and other typical components of the mass spectrometer, such as its ion detection, signal processing and readout systems, are collectively designated as MS in FIG. 1.
Inlet section 20 comprises a capillary tube 23 that serves as the sample inlet system of the mass spectrometer, and which conducts the LC column flow from a liquid chromatographic apparatus LC. In addition, a length of conduit 27 for directing a suitable nebulizing gas such as nitrogen into vaporization section 30 is coaxially disposed about capillary tube 23. Vaporization section 30 of APCI source 10 generally includes a vaporizing tube 33, a heater 35, and a conduit 37 for directing a suitable vaporizing gas such as nitrogen into vaporizing tube 33. Heater 35 is situated so as to ensure sufficient thermal contact with the wall of vaporizing tube 33. Capillary tube 23 is disposed along the central axis of vaporizing tube 33. A portion of vaporizing gas conduit 37 is coaxially disposed about nebulizing gas conduit 27 as well as capillary tube 23. Ionization section 40 of APCI source 10 generally includes an enclosed chamber (not specifically shown) into which an electrode, designated herein as a corona needle 43, is inserted. Corona needle 43 typically operates at about 5 kV to strike a low-current corona discharge 45 within ionization section 40.
In operation, a liquid sample comprising the LC column flow from liquid chromatographic apparatus LC is introduced into the heated vaporizing tube 33 via capillary tube 23. Nebulizing and vaporizing gas streams are introduced into vaporizing tube 33 through nebulizing gas conduit 27 and vaporizing gas conduit 37, respectively. The nebulizing gas flows concentrically around centrally disposed capillary tube 23 at high velocity flow, thereby nebulizing the liquid sample into small liquid droplets as the nebulizing gas and liquid sample enter vaporizing tube 33. Because the wall of vaporizing tube 33 is heated by heater 35 and consequently transfers heat energy into the interior of vaporizing tube 33, the liquid droplets of the nebulized sample entering vaporizing tube 33 are converted into vapor. The vaporizing gas is added to the system by means of vaporizing gas conduit 37 to assist in transporting the liquid droplet and vapor phases of the sample through vaporizing tube 33. The vapor then passes into the low-current corona discharge 45 established by corona needle 43 in ionization section 40, where the charge-neutral sample is ionized by ion molecule reactions with ions formed in the discharge.
In a typical configuration of conventional APCI source 10, vaporizing tube 33 has a 4-mm internal diameter and is 120-150 mm in length. A 1 ml/min liquid flow of sample-containing liquid corresponds to an approximately 1700 ml/min flow of vapor. The nebulizing gas flows at a rate of approximately 1000 ml/min, and the auxiliary vaporizing gas flows at a rate of approximately 1000-2000 ml/min. Thus, assuming a net gas flow rate of approximately 5000 ml/min through a 4-mm I.D., 120-mm long vaporizing tube 33, a droplet entrained in the gas, moving at the average flow velocity of the gas, would require approximately 15-20 ms to traverse the entire length of vaporizing tube 33. A liquid flow of 1 ml/min of water requires in excess of 40 W to heat and vaporize the water, neglecting any other heat losses. Because the flow through vaporizing tube 33 is laminar, the nebulized droplets will flow principally down the center of vaporizing tube 33 where the linear gas velocity is the greatest. It follows that the heat transfer from the heated wall of vaporizing tube 33 into the central gas flow is very inefficient, because it relies mostly on gas-phase heat transfer. Therefore, significantly higher temperatures at the wall of vaporizing tube 33 are required in order to transfer sufficient heat into the droplets. Unfortunately, the high temperature often thermally degrades the sample when the surrounding liquid is completely vaporized, thereby impeding the performance of mass spectrometer MS. On the other hand, if the heating temperature is reduced so as to avoid the deleterious effects of thermal degradation, incomplete vaporization of the sample can occur. As a consequence, non-vaporized droplets enter the ionization area, leading to problems in the ionization process and therefore inaccurate and/or uninterpretable mass analysis.
The present invention is provided to address, in whole or in part, these and other problems associated with the prior art.
In general terms, the present invention provides an apparatus and method for vaporizing a sample in a complete and uniform manner in order to optimize ionization of the sample in preparation for mass analysis thereof. The invention is particularly useful when implemented in an APCI ion source, which typically requires that the sample be vaporized by heat transfer means prior to ionization. The invention provides a gas conduit structured so as to define a flow path directed into a vaporization chamber along a vector that includes a velocity component tangential with respect to the central axis of the chamber. The gas so directed into the vaporization chamber establishes a vortex gas flow therein.
The sample is introduced into the vaporization chamber in a nebulized condition, and hence is characterized by a relatively broad, non-uniform mass (or, equivalently, size) distribution as in conventional systems. Accordingly, the nebulized sample flowing through the vaporization chamber consists of a range of large and small liquid droplets. Due to the vortex gas flow created in the vaporization chamber according to the present invention, however, the sample droplets are forced to flow toward a heated wall of the vaporization chamber. Given that force is proportional to mass, the larger droplets of the sample are subject to a greater force as compared to the smaller droplets. Thus, the larger droplets receive the greater proportion of heat energy supplied by the wall and, consequently, more energy is available for evaporating the larger droplets. At the same time, less energy is transferred to the smaller droplets. As a result, a sufficient amount of energy is available for evaporating the smaller droplets, but the energy transferred to the smaller droplets is not excessive enough to thermally degrade the analyte material of the smaller droplets. Therefore, overall vaporization of the sample is normalized, thereby optimizing subsequent ionization and mass analysis.
Moreover, because flow within the vaporization chamber is vortical, turbulent conditions within the vaporization chamber can be easily achieved, and an increase in gas flow rate will increase the capacity to vaporize all of the sample. By contrast, gas flow is laminar in conventional vaporization devices, such that a large portion of the nebulized sample flows linearly along the central axis of the vaporization space. Hence, an increase in gas flow rate in a conventional vaporization device can actually cause a decrease in its capacity to vaporize the sample due to reduced heat transfer.
Also, the present invention achieves improved vaporization without exposing the sample to potentially contaminating, catalytic, or non-inert surfaces. That is, no new surfaces or structures are added to the space where vaporization occurs. The sample does not contact the vortex-forming structures provided by the invention. The sample contacts only the inside surface of the heated wall of the vaporization chamber, which can be composed of quartz or other chemically inert material in the conventional manner. Additionally, the present invention does not reject or waste any of the sample during the sample introduction, vaporization, and nebulization processes, and accordingly is also useful for processing trace samples.
According to one embodiment of the present invention, an ion source is provided for use in mass spectrometry. The ion source comprises a chamber having a central axis, a sample conduit that includes a sample outlet communicating with the chamber, an ionizing device disposed downstream from the sample outlet, and a gas conduit that includes a gas outlet communicating with the chamber. The gas conduit defines a gas flow path directed into the chamber. The gas flow path includes a velocity component that is tangential with respect to the central axis of the chamber.
Preferably, the gas flow path also includes an axial component, and the sample flow path likewise includes an axial component, with both axial components being directed in a downstream direction through the chamber. In this manner, the gas also functions to assist in transporting the sample through the chamber.
The gas conduit in one embodiment comprises a helical channel that terminates at the gas outlet. The channel can be formed in various ways; examples are described hereinbelow. The embodiment can be structured such that the helical channel turns around a length of the sample conduit. In exemplary embodiments described in more detail hereinbelow, the helical channel is symmetrically or substantially symmetrically disposed around this length of the sample conduit. In other embodiments, the gas conduit comprises a plurality of helical channels, each of which terminates at a respective gas outlet into the chamber.
Preferably, the ion source also comprises a nebulizing fluid conduit to ensure adequate nebulization of the sample as it is introduced into the chamber. The nebulizing fluid conduit preferably includes a nebulizing fluid outlet that is adjacent and proximate to the sample outlet of the sample conduit. In embodiments described hereinbelow, the nebulizing fluid conduit is concentric to the sample outlet.
According to any of the embodiments described herein, the ion source can comprise a heating device disposed in thermal contact with the chamber that establishes a temperature gradient along the axial direction of the vaporization chamber. More heat energy is transferred to the sample at the upstream region of the chamber where more heat is needed for vaporization, and less energy is transferred at the downstream region where less heat is needed since vaporization is complete or substantially complete in the downstream region. Thus, for a heating device including an upstream end and a downstream end axially spaced from the upstream end, the thermal energy density provided by the heating device is at a substantial maximum at the upstream end and progressively reduces to a substantial minimum at the downstream end.
According to another embodiment of the present invention, an ion source for mass spectrometry comprises a vaporizing chamber having a central axis, a sample conduit including a sample outlet communicating with the chamber, a nebulizing gas conduit, and a vaporizing gas conduit. The nebulizing gas conduit includes a nebulizing gas outlet communicating with the chamber. A length of the nebulizing gas conduit is generally coaxially disposed about an axial length of the sample conduit. The vaporizing gas conduit is directed generally in a helical path about the sample conduit, and along the axial length of the sample conduit. The vaporizing gas conduit includes a vaporizing gas outlet communicating with the chamber. The vaporizing gas conduit defines a flow path directed into the chamber. The flow path includes a velocity component tangential with respect to the central axis of the vaporizing chamber.
The arrangement of the sample conduit and the nebulizing gas conduit with respect to the chamber, and particularly with respect to the central axis of the chamber, can be varied. Accordingly, in one embodiment, the respective lengths of the nebulizing gas conduit and the sample conduit are disposed along a sample introductory axis, and the sample introductory axis is substantially collinear with the central axis of the chamber. In an alternative embodiment, the sample introductory axis is generally radially offset from the central axis of the chamber. In a further alternative embodiment, the sample introductory axis is oriented at an angle with respect to the central axis of the chamber.
According to yet another embodiment of the present invention, an ion source for use in mass spectrometry comprises a vaporization chamber having a central axis, a sample conduit including a sample outlet communicating with the vaporization chamber, an ionization section disposed in flow communication with the vaporization chamber, and a vortex-forming section disposed upstream from the vaporization chamber. The vortex-forming section comprises an arcuate gas conduit that includes a gas outlet communicating with the vaporization chamber. The arcuate gas conduit defines a flow path directed into the vaporization chamber. The flow path includes a velocity component that is tangential with respect to the central axis.
A portion of the sample conduit can extend through the vortex-forming section, with the arcuate gas conduit turning around the sample conduit portion. The ion source can further comprise a nebulizing gas conduit that extends through the vortex-forming section in flow communication with the vaporization chamber.
In addition, the arcuate gas conduit can comprise a plurality of arcuate passages terminating at respective gas outlets, with each gas outlet communicating with the vaporization chamber. Each arcuate passage defines a respective gas flow path directed into the vaporization chamber through its respective gas outlet, and each gas flow path includes a velocity component tangential with respect to the central axis. Moreover, the vortex-forming section can comprise a manifold- or plenum-type structure that fluidly communicates with the arcuate passages.
The present invention also provides a method for vaporizing a sample in preparation for mass spectrometry according to the following steps. A chamber is provided that is defined by a wall radially disposed in relation to a central axis of the chamber. The chamber has an input end and an output end axially spaced from the input end. A sample is flowed into the chamber at the input end. The wall is heated to vaporize the sample. A vaporizing gas is tangentially flowed into the chamber to entrain the sample in a vortex gas flow and to thus force the sample to flow toward the heated wall, whereby vaporization of the sample is enhanced. The tangential flow can be accomplished by directing the vaporizing gas along one or more helical paths prior to introduction of the vaporizing gas into the chamber. The vaporized sample is flowed out from the chamber through the output end. The sample can then be ionized in preparation for subsequent mass analysis by mass spectrometer apparatus.